The present invention relates to optical fiber probes for sensing parameters simultaneously at different positions along the probe to provide a spatial profile of the parameters. More particularly, the invention relates to optical fiber probes for measuring multiple dosimetric parameters simultaneously at different positions along the probe in diagnostic and/or therapeutic applications related to photodynamic therapy.
Photodynamic therapy (PDT) dosimetry is currently based on two principal approaches, termed explicit and implicit dosimetry as discussed in for example Wilson B C, Patterson M S, Lilge L. (1997), Extrinsic and intrinsic Dosimetry For Photodynamic Therapy; Lasers in Medical Science 12: 182-199. For explicit dosimetry the three parameters governing PDT efficacy (fluence-rate, photosensitiser concentration, and molecular oxygen concentration) need to be monitored throughout the treatment volume. However, the current available fiber optic based dosimeters enable detection of parameters only at a single location, requiring several detectors, see for example Lilge L., Molpus K., Hasan T. and Wilson B. C., (1998) Intraperitoneal Photodynamic Therapy In A Murine Xenograft Model Of Human Epithelial Ovarian Carcinoma: Light Dosimetry And Biological Response, Photochem. Phtobiol. 83: 281-288, resulting in clinically unacceptable invasive procedures.
As described in previous work, Lilge L., Haw T., Willson B. C. (1993) Miniature Isotropic Optical Fibre Probes For Quantitative Light Dosimetry In Tissue, Phys. Med. Biol. 38: 215-230, fluence-rate detectors need to provide good sensitivity and isotropy of response in order to quantify the light intensity, called fluence-rate, in a turbid media such as tissue. Using fluorescent dyes with a fiber optic provides good response with isotropy provided by the inherently isotropic fluorescence emission by molecules. It was shown that the fluorescence intensity transmitted via the optical fiber to an opto-electronic detector is correlated to the fluence-rate at the position of the fluorophores inside the tissue. However, individual calibration of the optical fiber detector probe response is required prior to use. The efficiency and efficacy of such procedures would be enhanced by being able to monitor the radial dependence of fluence rate, photosensitizer fluorescence and molecular oxygen during the procedure.
Other use of lasers for therapeutic applications is well known, see for example Wilson B C. Wyman Dr, Malon E D, Tracy R, Farrell T (1991) Energy Delivery And Control For Interstitial Laser Hyperthemia And Laser Photocoagulation of Solid Tumors In Vivo; Proc. Soc. Photo-opt. Instr. Eng. 1599: 333-342. Here, the invention provides advantages through measuring the fluence rate profile, or for example, measuring the distribution of exogenous fluorophores.
U.S. Pat. No. 5,082,630 discloses a fiber probe for immuno-testing that uses fluorophore tags bound to an intermediate molecule which in turn is bound to a protein coating on a fiber core. A light beam from the fiber excites fluorescence in the fluorophores and when biomolecules being detected displace the fluorophores the fluorescent intensity decreases thereby indicating the presence of the biomolecules.
U.S. Pat. No. 5,275,160 shows a fiber probe with a single dye contained in a modified tip for radiance dosimetry. U.S. Pat. No. 5,483,958 shows a fiber optic probe using a solid state fluorescent probe joined to the end of the optical fiber.
U.S. Pat. No. 5,173,432 discloses a fiber optic sensor for the detection of pO2 using a luminescent dye encapsulated in a polymer matrix attached to the end of the optical fiber using an O2 permeable membrane.
U.S. Pat. No. 5,441,530 discloses a photochemotherapy dosimeter having a chemical cell at the end of the optical fiber and U.S. Pat. No. 5,851,225 discloses providing a laser probe for PDT applications having modified surface configurations for creating light emission at different wave lengths.
U.S. Pat. No. 5,837,196 discloses using an array of different biosensors comprised of biological binding partners to detect two or more different species of biological partners. This system relies upon a fiber bundle to convey the information to the detector from the distal ends of the fibers.
There is therefore a need for a single optical fiber probe capable of performing several independent tasks simultaneously.
It is an object of the present invention to provide a multitasking optical fiber probe, capable of measuring the fluence-rate, photosensitizer fluorescence and pO2 at several different positions along the probe and to provide increased information relevant to PDT dosimetry.
It is also an object of the present invention to provide an optical fiber probe that can be employed in other laser based therapeutic applications such as Barrett""s esophagus and interstitial laser hyperthermia.
An advantage of the multitasking probe of the present invention is that it can be used to provide the parameters required for PDT for the entire tissue volume in question. The probes of the present invention provide for measurement of a single parameter at multiple locations along the axis of a single optical fiber as well as providing for measurement of multiple parameters at multiple locations along the axis of the fiber.
In one aspect of the invention, there is provided an optical fiber probe comprising an optical fiber and at least one sensor zone spaced from an end of the optical fiber. The at least one sensor zone includes an effective photoactive constituent having an emission spectrum that emits light responsive to the photoactive constituent interacting with a preselected factor with some of the light being coupled into the optical fiber.
In another aspect, the present invention provides a multitasking optical fiber probe, comprising;
an optical fiber; and
at least two sensor zones spaced along a length of said optical fiber, each sensor zone including an effective photoactive constituent having an emission spectrum distinguishable in time domain or spectral domain from emission spectra of photoactive constituents in all other sensor zones, each photoactive constituent emitting light responsive to said photoactive constituent interacting with preselected factors with some of the light emitted from each sensor zone being coupled into the optical fiber.
In this aspect of the invention, the preselected factors are selected from the group consisting of radiation incident on said photoactive constituent in preselected wavelength bands and preselected molecules present in a volume adjacent to each sensor zone. The photoactive constituents in the at least two sensor zones may each be selected from the group consisting of fluorophore compounds each having a fluorescent emission spectrum, photoluminescent phosphor compounds each having a phosphorescent emission spectrum, chemiluminescent compounds each having a chemiluminescent spectrum, scintillator compounds each having a scintillator emission spectrum, and any combination thereof.
The present invention also provides a multitasking optical fiber probe apparatus, comprising:
a spectrophotometer;
an optical fiber probe connected to the spectrophotometer, the optical fiber probe including a longitudinal optical fiber, and at least two sensor zones spaced along a length of the optical fiber, each of the sensor zones including an effective photoactive constituent having an emission spectrum distinguishable in time domain or spectral domain from emission spectra of photoactive constituents in all other sensor zones, each photoactive constituent emitting light responsive to said photoactive constituent interacting with preselected factors; and
computer control means connected to the spectrophotometer for controlling the spectrophotometer and analyzing optical data from the optical fiber probe.
In another aspect of the invention there is provided a method of detection of factors including radiation and preselected molecules, comprising;
providing an optical fiber having a plurality of sensor zones spaced along a length of said optical fiber, each sensor zone including an effective photoactive constituent having an emission spectrum distinguishable in time domain or spectral domain from emission spectra of photoactive constituents in all other sensor zones, each photoactive constituent emitting light responsive to preselected factors interacting with said photoactive constituent with some of the emitted light being coupled into said optical fiber; and
deconvoluting emission spectrum from the photoactive constituent in each of said at least two sensor zones to determine a presence or absence of preselected factors interacting with said photoactive constituent in each sensor zone along the length of the fiber.